KINETICS AND MECHANISM OF CYCLIZATION OF SUBSTITUTED 2-(BENZOYLAMINO)ALKANAMIDES IN STRONGLY BASIC-MEDIUM

The cyclization reaction of substituted 2-(benzoylamino)alkanamides 1a -1i giving the corresponding substituted 2-phenylimidazol-4(5H)-ones 2 a-2i has been studied. The equilibrium constants of reactions of compo unds 1d-1f and -[(4-nitrobenzoyl)amino]-2,3-dimethylbutanenitrile (3) with methoxide have been determined in methanol-dimethyl sulfoxide med ia. For compound 1d and N-methyl derivatives 1a-1c, the cyclization ra te constants have been measured in dependence on methoxide concentrati on in media of varying contents of dimethyl sulfoxide. The cyclization reaction mechanism involves formation of anion in a rapid pre-equilib rium and subsequent rate-limiting step: either formation of a cyclic i ntermediate or splitting off of OH- ion from this intermediate. The pr oduct formed in the given medium is immediately transformed into its c onjugate base. A change in reaction medium affects the reactions of al l the compounds in the same way. The ratio of concentration of substra te to that of its anion at low methoxide concentrations is affected by the solvent composition (MeOH-DMSO). At higher methoxide and DMSO con centrations the reaction rate distinctly decreases, which can be inter preted by the transformation of reactive onion into non-reactive diani on. The corresponding N-methylbenzoylamino compounds are cyclized fast er by a factor of 400 as compared with compounds having no methyl grou p at the benzamide group.